1,256 research outputs found

    B cell heterogeneity in the teleost kidney: Evidence for a maturation gradient from anterior to posterior kidney

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    The fish immune system is quite different from the mammalian system because the anterior kidney forms the main site for hematopoiesis in this species. Using transcription factor-specific Abs derived from the murine system, together with anti-trout Ig Abs and Percoll gradient separation, we analyzed B cells from trout kidney sections and compared them to those from spleen and blood. For this study, immune cells were separated by Percoll gradients, and the resulting subpopulations were defined based on expression of B cell-specific transcription factors Pax-5 and B lymphocyte-induced maturation protein-1, as well as proliferative and Ig-secreting properties. Comparison of kidney, blood, and spleen B cell subsets suggest that 1) the anterior kidney contains mostly proliferating B cell precursors and plasma cells; 2) posterior kidney houses significant populations of (partially) activated B cells and plasmablasts; and 3) trout blood contains resting, non-Ig-secreting cells and lacks plasma cells. After LPS induction of resting B cells in vitro, the kidney and spleen have a high capacity for the generation of plasma cells, whereas the blood has virtually none. Our results indicate that trout B cell subsets are profoundly different among blood, anterior kidney, posterior kidney, and spleen. We hypothesize that developing B cells mature in the anterior side of the kidney and then migrate to sites of activation, either the spleen or the posterior kidney. Lastly, our data support the notion that the trout kidney is a complex, multifunctional immune organ with the potential to support both hemopoiesis as well as humoral immune activation

    Identification of a Novel Antiapoptotic Functional Domain in Simian Virus 40 Large T Antigen.

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    The ability of DNA tumor virus proteins to trigger apoptosis in mammalian cells is well established. For example, transgenic expression of a simian virus 40 (SV40) T-antigen N-terminal fragment (N-termTag) is known to induce apoptosis in choroid plexus epithelial cells. SV40 T-antigen-induced apoptosis has generally been considered to be a p53-dependent event because cell death in the brain is greatly diminished in a p53-/- background strain and is abrogated by expression of wild-type (p53-binding) SV40 T antigen. We now show that while N-termTags triggered apoptosis in rat embryo fibroblasts cultured in low serum, expression of full-length T antigens unable to bind p53 [mut(p53-)Tags] protected against apoptosis without causing transformation. One domain essential for blocking apoptosis by T antigen was mapped to amino acids 525 to 541. This domain has \u3e60% homology with a domain of adenovirus type 5 E1B 19K required to prevent E1A-induced apoptosis. In the context of both wild-type T antigen and mut(p53-)Tags, mutation of two conserved amino acids in this region eliminated T antigen\u27s antiapoptotic activity in REF-52 cells. These data suggest that SV40 T antigen contains a novel functional domain involved in preventing apoptosis independently of inactivation of p53

    An investigation of psychological type and career maturity

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    The problem addressed by this research was to investigate Super's construct of career maturity, as defined by the Career Development Inventory, to determine if its development is limited to a certain psychological type, as defined by the Myers-Briggs Type Indicator. The Hotelling-Lawley Trace was the statistic employed to analyze the potential relationships between the scales of the Career Development Inventory and the Myers-Briggs Type Indicator. It was determined that there were no statistically significant correlations between the scales of the two instruments. Results indicate that the concept of career maturity is more broadly defined than theory currently states. Career counselors should accept different psychological type preferences as effective processes for making credible career decisions. The results of this investigation suggest the need for a reconsideration of three basic tenets of Super's theoretical model of career development. The model should be reconsidered for the purpose of broadening the definition of acceptable processes of information gathering, decision making, and decision strategy in the course of career decision making

    ā€œIt Hurts a Latina When They Tell Us Anything About Our Childrenā€: Implications of Mexican-Origin Mothers' Maternal Identities, Aspirations, and Attitudes About Cultural Transmission for Childhood Obesity Prevention

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    Background: This qualitative study explored values, attitudes, and beliefs held by Mexican-origin mothers of preschool-aged children to enhance understanding of cultural influences on behaviors associated with childhood obesity risk. Methods: During face-to-face interviews, 39 Mexican-origin mothers of preschool-aged children discussed their hopes for their children, their image of the perfect mother, Mexican and American foods, why they taught their children about these foods, and their opinions about television (TV) viewing language. Results: Participants wanted their children to become successful, ?good? people, which necessitated doing well in school. Mothers also wanted their children to know them, which required understanding the mothers' Mexican backgrounds. Mothers wanted their children to maintain Mexican values and identities. Some mothers viewed American culture as harmful. Many participants prepared their child for going to Mexico by exposing them to Mexican culture and foods. Some mothers fed their children American foods to prepare them for school. Perceptions of American foods generally reflected stereotypical unhealthy foods. TV helped teach children Spanish and English. Being a good mother was core to participants' identities; thus, hearing about child overweight made some mothers feel like failures. Conclusions: Health promotion programs may be more salient to mothers if they: underscore how a healthy weight can help children in school; teach mothers to prepare healthy American foods that their children will encounter in kindergarten; assist mothers in teaching their children about Mexico; and present information about childhood obesity in ways that reinforce what mothers are doing well, enhance mothers' self-efficacy, and allay feelings of failure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140339/1/chi.2015.0011.pd

    Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid

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    Objectives A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells. Methods Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6 h. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations and single-cell RNA-seq, and ELISA and LEGENDplex analysis of PsA SF were also performed. Results We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of any in vitro stimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be amongst those most highly upregulated by PsA monocytes/macrophages; and both proteins were elevated in PsA SF. Conclusions Using multiomic analyses we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance. Competing Interest Statement The authors have declared no competing interest

    Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid

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    Objectives: A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells. Methods: Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6ā€‰hours. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations, single-cell RNA-seq, ELISA and LEGENDplex analysis of PsA SF were also performed. Results: We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of any in vitro stimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be among those most highly upregulated by PsA monocytes/macrophages in SF; and both proteins were elevated in PsA SF. Conclusions: Using multiomic analyses, we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance

    The impact of COVID-19 public health restrictions on particulate matter pollution measured by a validated low-cost sensor network in Oxford, UK

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    Emergency responses to the COVID-19 pandemic led to major changes in travel behaviours and economic activities with arising impacts upon urban air quality. To date, these air quality changes associated with lockdown measures have typically been assessed using limited city-level regulatory monitoring data, however, low-cost air quality sensors provide capabilities to assess changes across multiple locations at higher spatial-temporal resolution, thereby generating insights relevant for future air quality interventions. The aim of this study was to utilise high-spatial resolution air quality information utilising data arising from a validated (using a random forest field calibration) network of 15 low-cost air quality sensors within Oxford, UK to monitor the impacts of multiple COVID-19 public heath restrictions upon particulate matter concentrations (PM10, PM2.5) from January 2020 to September 2021. Measurements of PM10 and PM2.5 particle size fractions both within and between site locations are compared to a pre-pandemic related public health restrictions baseline. While average peak concentrations of PM10 and PM2.5 were reduced by 9ā€“10 Ī¼g/m3 below typical peak levels experienced in recent years, mean daily PM10 and PM2.5 concentrations were only āˆ¼1 Ī¼g/m3 lower and there was marked temporal (as restrictions were added and removed) and spatial variability (across the 15-sensor network) in these observations. Across the 15-sensor network we observed a small local impact from traffic related emission sources upon particle concentrations near traffic-oriented sensors with higher average and peak concentrations as well as greater dynamic range, compared to more intermediate and background orientated sensor locations. The greater dynamic range in concentrations is indicative of exposure to more variable emission sources, such as road transport emissions. Our findings highlight the great potential for low-cost sensor technology to identify highly localised changes in pollutant concentrations as a consequence of changes in behaviour (in this case influenced by COVID-19 restrictions), generating insights into non-traffic contributions to PM emissions in this setting. It is evident that additional non-traffic related measures would be required in Oxford to reduce the PM10 and levels to within WHO health-based guidelines and to achieve compliance with PM2.5 targets developed under the Environment Act 2021
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